Screening, Surveillance, and Testing for GI Cancers

The Screening, Surveillance, and Molecular Testing for Gastrointestinal Cancers session of the 2012 AGA Spring Postgraduate Course contained five outstanding speakers who discussed cancers of the gastrointestinal tract or their precursor lesions, which gastroenterologists face frequently in the clinic.

Dr. John Inadomi from the University of Washington, Seattle, highlighted some evidence-based and practical approaches to care for patients who have developed or are at risk for Barrett’s esophagus.

Dr. Inadomi pointed out that our approach to screening should only involve those patients with multiple risk factors, such as white males with chronic heartburn and acid reflux, tobacco usage, and increased central obesity. Once Barrett’s is detected, there is low effectiveness of surveillance for Barrett’s to reduce esophageal cancer mortality, and is not cost-effective. This is largely due to the low observed conversion of Barrett’s esophagus to esophageal adenocarcinoma (less than 0.5% of patients/year), and that surveillance relies on repeated measures of a poor marker (i.e. random biopsies). Endoscopic ablation therapy is largely reserved for those patients with high-grade dysplasia (HGD), some patients with low-grade dysplasia (LGD), and is not for those with non-dysplastic Barrett’s esophagus. Ablation of patients with HGD and as well as some patients with LGD is cost-effective and may decrease cancer incidence. Dr. Inadomi also presented some new approaches for the management of Barrett’s and its potential complications, included advanced imaging techniques, the use of molecular diagnostics, and chemoprevention.

Dr. Asif Khalid from the University of Pittsburgh presented an approach to evaluation and care of the patient with cystic lesions of the pancreas. Dr. Khalid pointed out that serous cystic tumors are largely benign, are equal among males and females, and often have a central scar or honeycomb pattern on imaging. Mucinous neoplasms are a different story, and need to be carefully evaluated for potential resection. The mucinous cystic neoplasm (MCN) is premalignant, occurs more commonly in females, may present with septations on imaging, produces carcinoembryonic antigen (CEA), and needs resection. Intraductal papillary mucinous neoplasms (IPMNs) can be main duct, which requires resection as the only curative option, or branch duct, and requires surgical resection if at least 3 cm. IPMNs are equal between males and females, produce CEA, and may demonstrate mutation in the GNAS gene. Diagnostic differentiation between lesions can be challenging, but with imaging (endoscopic ultrasound, MRI, and CT) and aspiration of the lesion for cytology, amylase, CEA, and other molecular markers, differentiation is possible. Dr. Khalid stated that key features that differentiate mucinous from non-mucinous lesions are the presence of mutant KRAS and elevated CEA levels in the aspirate, and the presence of allelic loss in DNA taken in the sample. He also pointed out that key features to help differentiate malignant from non-malignant lesions include high DNA content, mutant KRAS, and allelic loss.

Dr. Hashem El-Serag from Baylor College of Medicine, Houston, showcased information on hepatocellular carcinoma (HCC). He showed evidence that the incidence of HCC is increasing, and that survival from HCC is marginally increasing as well with improved approaches to care. Dr. El-Serag reviewed the Milan criteria, where a person is potentially curative by resection or liver transplant if there are three or fewer nodules that are 3 cm or less in diameter. Dr. El-Serag presented data showing that surveillance for HCC reduces mortality from HCC. Efforts should be focused on Asian hepatitis B carriers, those with a family history of HCC, blacks from Africa, and patients with cirrhosis who have hepatitis B or C. Surveillance should be done every 6 months, and the combined use of ultrasound (with a sensitivity of 72%) with alpha-fetoprotein (AFP) is the best studied. Other biomarkers in the literature for HCC screening include des-gamma-carboxy prothrombin (DCP), golgi protein-73, and osteopontin. Dr. El-Serag also reviewed key aspects of imaging criteria for identifying HCC in cirrhotic patients, which includes hyper-enhancement by two imaging techniques if a lesion is at least 1 cm but less than 2 cm in diameter, and by one imaging technique if 2 cm or greater, with or without liver biopsy if the appearance is atypical.

Dr. Douglas Rex from Indiana University, Indianapolis, highlighted several quality issues in regard to screening for colorectal cancer. He stated that the primary contribution of gastroenterologists to colorectal cancer prevention is high quality colonoscopy. Dr. Rex pointed out recent evidence that colonoscopy is less effective in the right colon, compared with the left colon, and one contribution to this is the right-sided location of serrated, flat, and depressed lesions that blend in with the surrounding mucosa. For all colorectal screening tests, there is limited evidence regarding sensitivity for serrated lesions. Dr. Rex provided evidence that guaiac-based fecal occult blood test (FOBT) screening should all be now converted to fecal immunohistochemical test (FIT) screening due to enhanced sensitivity of the FIT tests. Dr. Rex also provided initial data on the first serum-screening assay for colorectal cancer, which was unable to detect precancerous lesions.

Dr. Sapna Syngal from the Dana-Farber Cancer Center in Boston presented on hereditary colorectal cancer syndromes. These syndromes elevate the risk for colorectal cancer, and if they are not recognized, their associated cancers present with a young age of onset. Patients and potential patients need to be referred for genetic counseling and testing, particularly those who present at a young age, have a high number of polyps, show upper GI lesions, and have strong family history of cancer or polyps. Dr. Syngal highlighted the issue of "genetic malpractice" that is growing in the United States due to a lack of recognition and referral for evaluation. These syndromes are managed much differently than sporadic cancer in their approach to surgery, surveillance for associated cancers, the screening of family members, and reproductive counseling and prenatal testing.

Dr. Syngal reviewed familial adenomatous polyposis (FAP), an autosomal dominant condition, and highlighted MYH associated polyposis (MAP), an autosomal recessive condition. Both FAP and MAP can present with colon polyps and cancer, upper GI lesions, form desmoid tumors, and are associated with thyroid, brain, and osteoma tumors. Care is through colectomy, upper GI surveillance, and chemoprevention for any lower GI remnant. Dr. Syngal also highlighted Lynch syndrome, which is associated with tumors of the colon and upper GI track, female reproductive track, urinary track, and sebaceous skin tumors. Lynch syndrome patients can undergo colonoscopic surveillance and subsequent colectomy, as well as endometrial aspiration and subsequent total abdominal hysterectomy-bilateral salpingo-oophorectomy. Dr. Syngal reviewed testing of tumors for microsatellite instability and immunohistochemistry for the DNA mismatch repair genes (mutation of which cause Lynch syndrome) and discussed prediction models for germline testing.

John M. Carethers, M.D., is the John G. Searle Professor and chair of the department of internal medicine at the University of Michigan, Ann Arbor.

The Screening, Surveillance, and Molecular Testing for Gastrointestinal Cancers session of the 2012 AGA Spring Postgraduate Course contained five outstanding speakers who discussed cancers of the gastrointestinal tract or their precursor lesions, which gastroenterologists face frequently in the clinic.

Dr. John Inadomi from the University of Washington, Seattle, highlighted some evidence-based and practical approaches to care for patients who have developed or are at risk for Barrett’s esophagus.

Dr. Inadomi pointed out that our approach to screening should only involve those patients with multiple risk factors, such as white males with chronic heartburn and acid reflux, tobacco usage, and increased central obesity. Once Barrett’s is detected, there is low effectiveness of surveillance for Barrett’s to reduce esophageal cancer mortality, and is not cost-effective. This is largely due to the low observed conversion of Barrett’s esophagus to esophageal adenocarcinoma (less than 0.5% of patients/year), and that surveillance relies on repeated measures of a poor marker (i.e. random biopsies). Endoscopic ablation therapy is largely reserved for those patients with high-grade dysplasia (HGD), some patients with low-grade dysplasia (LGD), and is not for those with non-dysplastic Barrett’s esophagus. Ablation of patients with HGD and as well as some patients with LGD is cost-effective and may decrease cancer incidence. Dr. Inadomi also presented some new approaches for the management of Barrett’s and its potential complications, included advanced imaging techniques, the use of molecular diagnostics, and chemoprevention.

Dr. Asif Khalid from the University of Pittsburgh presented an approach to evaluation and care of the patient with cystic lesions of the pancreas. Dr. Khalid pointed out that serous cystic tumors are largely benign, are equal among males and females, and often have a central scar or honeycomb pattern on imaging. Mucinous neoplasms are a different story, and need to be carefully evaluated for potential resection. The mucinous cystic neoplasm (MCN) is premalignant, occurs more commonly in females, may present with septations on imaging, produces carcinoembryonic antigen (CEA), and needs resection. Intraductal papillary mucinous neoplasms (IPMNs) can be main duct, which requires resection as the only curative option, or branch duct, and requires surgical resection if at least 3 cm. IPMNs are equal between males and females, produce CEA, and may demonstrate mutation in the GNAS gene. Diagnostic differentiation between lesions can be challenging, but with imaging (endoscopic ultrasound, MRI, and CT) and aspiration of the lesion for cytology, amylase, CEA, and other molecular markers, differentiation is possible. Dr. Khalid stated that key features that differentiate mucinous from non-mucinous lesions are the presence of mutant KRAS and elevated CEA levels in the aspirate, and the presence of allelic loss in DNA taken in the sample. He also pointed out that key features to help differentiate malignant from non-malignant lesions include high DNA content, mutant KRAS, and allelic loss.

Dr. Hashem El-Serag from Baylor College of Medicine, Houston, showcased information on hepatocellular carcinoma (HCC). He showed evidence that the incidence of HCC is increasing, and that survival from HCC is marginally increasing as well with improved approaches to care. Dr. El-Serag reviewed the Milan criteria, where a person is potentially curative by resection or liver transplant if there are three or fewer nodules that are 3 cm or less in diameter. Dr. El-Serag presented data showing that surveillance for HCC reduces mortality from HCC. Efforts should be focused on Asian hepatitis B carriers, those with a family history of HCC, blacks from Africa, and patients with cirrhosis who have hepatitis B or C. Surveillance should be done every 6 months, and the combined use of ultrasound (with a sensitivity of 72%) with alpha-fetoprotein (AFP) is the best studied. Other biomarkers in the literature for HCC screening include des-gamma-carboxy prothrombin (DCP), golgi protein-73, and osteopontin. Dr. El-Serag also reviewed key aspects of imaging criteria for identifying HCC in cirrhotic patients, which includes hyper-enhancement by two imaging techniques if a lesion is at least 1 cm but less than 2 cm in diameter, and by one imaging technique if 2 cm or greater, with or without liver biopsy if the appearance is atypical.

Dr. Douglas Rex from Indiana University, Indianapolis, highlighted several quality issues in regard to screening for colorectal cancer. He stated that the primary contribution of gastroenterologists to colorectal cancer prevention is high quality colonoscopy. Dr. Rex pointed out recent evidence that colonoscopy is less effective in the right colon, compared with the left colon, and one contribution to this is the right-sided location of serrated, flat, and depressed lesions that blend in with the surrounding mucosa. For all colorectal screening tests, there is limited evidence regarding sensitivity for serrated lesions. Dr. Rex provided evidence that guaiac-based fecal occult blood test (FOBT) screening should all be now converted to fecal immunohistochemical test (FIT) screening due to enhanced sensitivity of the FIT tests. Dr. Rex also provided initial data on the first serum-screening assay for colorectal cancer, which was unable to detect precancerous lesions.

Dr. Sapna Syngal from the Dana-Farber Cancer Center in Boston presented on hereditary colorectal cancer syndromes. These syndromes elevate the risk for colorectal cancer, and if they are not recognized, their associated cancers present with a young age of onset. Patients and potential patients need to be referred for genetic counseling and testing, particularly those who present at a young age, have a high number of polyps, show upper GI lesions, and have strong family history of cancer or polyps. Dr. Syngal highlighted the issue of "genetic malpractice" that is growing in the United States due to a lack of recognition and referral for evaluation. These syndromes are managed much differently than sporadic cancer in their approach to surgery, surveillance for associated cancers, the screening of family members, and reproductive counseling and prenatal testing.

Dr. Syngal reviewed familial adenomatous polyposis (FAP), an autosomal dominant condition, and highlighted MYH associated polyposis (MAP), an autosomal recessive condition. Both FAP and MAP can present with colon polyps and cancer, upper GI lesions, form desmoid tumors, and are associated with thyroid, brain, and osteoma tumors. Care is through colectomy, upper GI surveillance, and chemoprevention for any lower GI remnant. Dr. Syngal also highlighted Lynch syndrome, which is associated with tumors of the colon and upper GI track, female reproductive track, urinary track, and sebaceous skin tumors. Lynch syndrome patients can undergo colonoscopic surveillance and subsequent colectomy, as well as endometrial aspiration and subsequent total abdominal hysterectomy-bilateral salpingo-oophorectomy. Dr. Syngal reviewed testing of tumors for microsatellite instability and immunohistochemistry for the DNA mismatch repair genes (mutation of which cause Lynch syndrome) and discussed prediction models for germline testing.

John M. Carethers, M.D., is the John G. Searle Professor and chair of the department of internal medicine at the University of Michigan, Ann Arbor.

The Screening, Surveillance, and Molecular Testing for Gastrointestinal Cancers session of the 2012 AGA Spring Postgraduate Course contained five outstanding speakers who discussed cancers of the gastrointestinal tract or their precursor lesions, which gastroenterologists face frequently in the clinic.

Dr. John Inadomi from the University of Washington, Seattle, highlighted some evidence-based and practical approaches to care for patients who have developed or are at risk for Barrett’s esophagus.

Dr. Inadomi pointed out that our approach to screening should only involve those patients with multiple risk factors, such as white males with chronic heartburn and acid reflux, tobacco usage, and increased central obesity. Once Barrett’s is detected, there is low effectiveness of surveillance for Barrett’s to reduce esophageal cancer mortality, and is not cost-effective. This is largely due to the low observed conversion of Barrett’s esophagus to esophageal adenocarcinoma (less than 0.5% of patients/year), and that surveillance relies on repeated measures of a poor marker (i.e. random biopsies). Endoscopic ablation therapy is largely reserved for those patients with high-grade dysplasia (HGD), some patients with low-grade dysplasia (LGD), and is not for those with non-dysplastic Barrett’s esophagus. Ablation of patients with HGD and as well as some patients with LGD is cost-effective and may decrease cancer incidence. Dr. Inadomi also presented some new approaches for the management of Barrett’s and its potential complications, included advanced imaging techniques, the use of molecular diagnostics, and chemoprevention.

Dr. Asif Khalid from the University of Pittsburgh presented an approach to evaluation and care of the patient with cystic lesions of the pancreas. Dr. Khalid pointed out that serous cystic tumors are largely benign, are equal among males and females, and often have a central scar or honeycomb pattern on imaging. Mucinous neoplasms are a different story, and need to be carefully evaluated for potential resection. The mucinous cystic neoplasm (MCN) is premalignant, occurs more commonly in females, may present with septations on imaging, produces carcinoembryonic antigen (CEA), and needs resection. Intraductal papillary mucinous neoplasms (IPMNs) can be main duct, which requires resection as the only curative option, or branch duct, and requires surgical resection if at least 3 cm. IPMNs are equal between males and females, produce CEA, and may demonstrate mutation in the GNAS gene. Diagnostic differentiation between lesions can be challenging, but with imaging (endoscopic ultrasound, MRI, and CT) and aspiration of the lesion for cytology, amylase, CEA, and other molecular markers, differentiation is possible. Dr. Khalid stated that key features that differentiate mucinous from non-mucinous lesions are the presence of mutant KRAS and elevated CEA levels in the aspirate, and the presence of allelic loss in DNA taken in the sample. He also pointed out that key features to help differentiate malignant from non-malignant lesions include high DNA content, mutant KRAS, and allelic loss.

Dr. Hashem El-Serag from Baylor College of Medicine, Houston, showcased information on hepatocellular carcinoma (HCC). He showed evidence that the incidence of HCC is increasing, and that survival from HCC is marginally increasing as well with improved approaches to care. Dr. El-Serag reviewed the Milan criteria, where a person is potentially curative by resection or liver transplant if there are three or fewer nodules that are 3 cm or less in diameter. Dr. El-Serag presented data showing that surveillance for HCC reduces mortality from HCC. Efforts should be focused on Asian hepatitis B carriers, those with a family history of HCC, blacks from Africa, and patients with cirrhosis who have hepatitis B or C. Surveillance should be done every 6 months, and the combined use of ultrasound (with a sensitivity of 72%) with alpha-fetoprotein (AFP) is the best studied. Other biomarkers in the literature for HCC screening include des-gamma-carboxy prothrombin (DCP), golgi protein-73, and osteopontin. Dr. El-Serag also reviewed key aspects of imaging criteria for identifying HCC in cirrhotic patients, which includes hyper-enhancement by two imaging techniques if a lesion is at least 1 cm but less than 2 cm in diameter, and by one imaging technique if 2 cm or greater, with or without liver biopsy if the appearance is atypical.

Dr. Douglas Rex from Indiana University, Indianapolis, highlighted several quality issues in regard to screening for colorectal cancer. He stated that the primary contribution of gastroenterologists to colorectal cancer prevention is high quality colonoscopy. Dr. Rex pointed out recent evidence that colonoscopy is less effective in the right colon, compared with the left colon, and one contribution to this is the right-sided location of serrated, flat, and depressed lesions that blend in with the surrounding mucosa. For all colorectal screening tests, there is limited evidence regarding sensitivity for serrated lesions. Dr. Rex provided evidence that guaiac-based fecal occult blood test (FOBT) screening should all be now converted to fecal immunohistochemical test (FIT) screening due to enhanced sensitivity of the FIT tests. Dr. Rex also provided initial data on the first serum-screening assay for colorectal cancer, which was unable to detect precancerous lesions.

Dr. Sapna Syngal from the Dana-Farber Cancer Center in Boston presented on hereditary colorectal cancer syndromes. These syndromes elevate the risk for colorectal cancer, and if they are not recognized, their associated cancers present with a young age of onset. Patients and potential patients need to be referred for genetic counseling and testing, particularly those who present at a young age, have a high number of polyps, show upper GI lesions, and have strong family history of cancer or polyps. Dr. Syngal highlighted the issue of "genetic malpractice" that is growing in the United States due to a lack of recognition and referral for evaluation. These syndromes are managed much differently than sporadic cancer in their approach to surgery, surveillance for associated cancers, the screening of family members, and reproductive counseling and prenatal testing.

Dr. Syngal reviewed familial adenomatous polyposis (FAP), an autosomal dominant condition, and highlighted MYH associated polyposis (MAP), an autosomal recessive condition. Both FAP and MAP can present with colon polyps and cancer, upper GI lesions, form desmoid tumors, and are associated with thyroid, brain, and osteoma tumors. Care is through colectomy, upper GI surveillance, and chemoprevention for any lower GI remnant. Dr. Syngal also highlighted Lynch syndrome, which is associated with tumors of the colon and upper GI track, female reproductive track, urinary track, and sebaceous skin tumors. Lynch syndrome patients can undergo colonoscopic surveillance and subsequent colectomy, as well as endometrial aspiration and subsequent total abdominal hysterectomy-bilateral salpingo-oophorectomy. Dr. Syngal reviewed testing of tumors for microsatellite instability and immunohistochemistry for the DNA mismatch repair genes (mutation of which cause Lynch syndrome) and discussed prediction models for germline testing.

John M. Carethers, M.D., is the John G. Searle Professor and chair of the department of internal medicine at the University of Michigan, Ann Arbor.